BCR-ABL1 Transcript Type Predicts Outcomes After Imatinib in CML

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Study results suggest that the e13a2 BCR-ABL1 fusion transcript is associated with poorer clinical outcomes than the e14a2 transcript.
Study results suggest that the e13a2 BCR-ABL1 fusion transcript is associated with poorer clinical outcomes than the e14a2 transcript.

The e14a2 BCR-ABL1 transcript was associated with earlier response and prolonged progression-free (PFS) and overall survival (OS) after imatinib treatment among patients with chronic myeloid leukemia (CML), according to a study published in the American Journal of Hematology.1

Little is known about the importance of the BCR-ABL1 transcript type in this setting. This retrospective analysis included 559 patients with Philadelphia (Ph) chromosome-positive and/or BCR-ABL1-positive CML from 3 concurrent prospective studies.

The baseline characteristics were similar between cohorts, except 66% and 57% of patients in the e13a2 and e14a2 cohorts were male, respectively (P = .050). The e13a2 and e14a2 transcripts were present in 36% and 52% of patients, respectively.

Though the complete cytogenetic response rates (CCyRR) were similar at 12 months, the e14a2 cohort had significantly higher MMR rates at 18 months (67% vs 52%; P = .001) and MR4.0 rates at 36 months (30% vs 20%; P = .013) compared with the e13a2 cohort.

The median time to CCyRR was also similar between groups. The median time to MMR and MR4.0, however, was significantly shorter with the e14a2 transcript compared with the e13a2 transcript (6 vs 12 months and 41 vs 61 months, respectively).

The 7-year estimated probabilities of PFS was 89% and 81% in the e14a2 and e13a2 cohorts, respectively (P = .005), and 90% and 83%, respectively for OS (P = .017).

RELATED: Characterizing Therapy-persistent Leukemic Stem Cells in CML

These results suggest that the e13a2 BCR-ABL1 fusion transcript is associated with poorer clinical outcomes than the e14a2 transcript. The authors wrote that “including the transcript type in the calculation of the baseline risk scores may improve prognostic stratification and may help the choice of the best treatment.”

Reference

  1. Castagnetti F, Gugliotta G, Breccia M, et al. The BCR-ABL 1 transcript type influences response and outcome in Philadelphia chromosome-positive chronic myeloid leukemia patients treated frontline with imatinib. Am J Hematol. In press.

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